Addison's disease - Symptoms and causes

Addison's disease (primary adrenal insufficiency) is a rare disorder where the adrenal glands, located on top of each kidney, fail to produce enough of two critical hormones: cortisol and aldosterone.

Cortisol helps regulate metabolism, blood pressure, immune response, and the body's reaction to stress. Aldosterone maintains sodium and potassium balance, which directly influences blood volume and pressure. 

When the adrenal cortex (outer layer of the adrenal gland) is damaged—most commonly due to an autoimmune reaction or infection—it leads to a gradual but progressive loss of hormone production.

This condition affects everyone of all ages & genders, and it develops gradually over time. 

However, under stress such as infection or injury, it can lead to a life-threatening crisis due to sudden hormone deficiency.

Who is at Risk of Developing Addison's Disease?

Addison's disease can affect individuals of any age, but it is most commonly diagnosed in people between the ages of 30 and 50. Both men and women are equally affected. The condition is more likely to occur in people with autoimmune diseases, namely type 1 diabetes, autoimmune thyroid disease (like Hashimoto's thyroiditis), or vitiligo, as the immune system may mistakenly attack the adrenal glands. It can also occur in patients with a history of tuberculosis or being treated for the same.

A personal or family history of autoimmune conditions increases the risk of developing these conditions. It can also develop as a result of infections that damage the adrenal glands, namely tuberculosis, HIV, or fungal infections. 

However, this is less common today, especially in developed countries. In rare cases, Addison's disease may occur due to genetic disorders, adrenal gland surgery, cancer spreading to the adrenal glands, or prolonged use of certain medications that suppress adrenal function.

Key Signs and Symptoms of Addison's Disease

• Fatigue
• Muscle weakness
• Unintentional weight loss
• Loss of appetite
• Darkening of the skin (especially in scars, creases, and gums)
• Low blood pressure
• Salt cravings
• Nausea or vomiting
• Abdominal pain
• Diarrhea or constipation
• Low blood sugar (hypoglycemia)
• Irritability or depression
• Joint or muscle pain
• Dizziness or fainting
• Irregular or absent menstrual periods in women

Why does Addison's Disease happen?

The most common cause of Addison's disease is autoimmune adrenalitis, in which the immune system mistakenly attacks the adrenal cortex, leading to gradual destruction of the hormone-producing cells. This accounts for the majority of cases in developed countries.

Other causes include infections, such as tuberculosis, which can directly damage the adrenal glands. Less commonly, Addison's disease can result from metastatic cancer, bleeding into the adrenal glands (adrenal hemorrhage), or genetic conditions like congenital adrenal hyperplasia or adrenoleukodystrophy. 

Surgical removal of the adrenal glands or long-term use of certain antifungal or steroid medications that interfere with adrenal hormone production can also trigger the condition.

How is Addison's Disease Diagnosed?

• Medical history & physical exam: Review of symptoms, blood pressure, skin changes, and personal/family history of autoimmune disease.
• Blood tests: Measure cortisol, ACTH (adrenocorticotropic hormone), sodium, potassium, glucose, and aldosterone levels.
• ACTH stimulation test: This test assesses how well the adrenal glands respond to synthetic ACTH; a limited or no rise in cortisol confirms the diagnosis.
• Insulin-induced hypoglycemia test (when needed): Evaluates pituitary function by checking cortisol response to low blood sugar.
• Plasma renin activity test: Measures renin levels to evaluate aldosterone deficiency and fluid balance.
• Autoantibody tests: Detect adrenal antibodies to confirm autoimmune origin.
• Imaging tests: CT scan of the abdomen to check adrenal size, structure, and look for infections, cancer, or bleeding.
• MRI of the pituitary gland: Performed if secondary adrenal insufficiency is suspected due to pituitary disorders.

How is Addison’s Disease Treated?

• Daily hormone replacement therapy: Long-term use of synthetic corticosteroids to replace missing cortisol and aldosterone.
• Oral hydrocortisone or prednisone: Taken in specific doses, usually twice daily, to mimic the body’s natural cortisol rhythm.
• Fludrocortisone acetate: Replaces aldosterone and helps maintain sodium & potassium balance, as well as blood pressure.
• Increased salt intake: Often recommended, especially during hot weather or physical activity.
• Adjusting medication during stress or illness: Temporary increase in steroid dose during infections, surgery, or injury to prevent adrenal crisis.
• Injectable corticosteroids: Emergency use in patients who cannot take oral medication due to vomiting or during an adrenal crisis.
• Medical alert identification: Wearing a bracelet or carrying a card to inform healthcare providers in emergencies.
• Regular follow-ups: Monitoring hormone levels and adjusting medication as needed.

Managing Life with Addison’s Disease

Managing Addison’s disease requires daily attention and lifelong adherence to hormone replacement therapy. Patients must take their medications as prescribed and never skip doses, as even a short interruption can trigger symptoms or an adrenal crisis. 

In the time of physical or emotional stress, such as illness, surgery, or injury, medication doses often need to be increased to meet the body’s elevated demand for cortisol. It’s important to recognize early warning signs of under-replacement, such as fatigue or dizziness, and respond promptly. Carrying an emergency corticosteroid injection kit is essential for situations where oral medication can’t be taken. 

Patients should also stay hydrated, monitor blood pressure, and, if advised by their doctor, maintain a diet with sufficient salt. Routine medical check-ups are crucial for monitoring hormone levels and adjusting treatment accordingly. 

Education plays a crucial role—patients and their close contacts should be trained to recognize the symptoms of adrenal crisis and respond promptly. Wearing a medical ID bracelet helps ensure that proper care is received in the event of an emergency.

🩺 Sick Day Rules for Addison’s Disease

1️⃣ If you are unwell (fever, cold, infection, minor illness), double your usual steroid dose until you recover.

2️⃣ Keep taking your fludrocortisone (if prescribed) at the usual dose.

3️⃣ If you are vomiting, unable to keep medicines down, or feel very weak/dizzy, take your emergency injection (hydrocortisone 100 mg IM/SC) immediately.

4️⃣ After the injection, go to the nearest hospital immediately for further treatment.

5️⃣ Always carry a steroid emergency card and inform healthcare workers about your Addison’s disease.

6️⃣ If you are having surgery or a procedure, inform your doctor beforehand so they can give you extra steroids.

7️⃣ Keep a supply of oral steroids and injectable hydrocortisone at home.

8️⃣ Drink plenty of fluids and monitor for dizziness, extreme fatigue, or confusion.

9️⃣ Never stop taking your steroids suddenly.

🔟 Teach family/friends how to give the emergency injection in case you cannot do it yourself.